Avian arthritis/tenosynovitis, a disease closely resembling human rheumatoid arthritis, has been shown to result from naturally-acquired reovirus infection. Viruses of this group are endemic in the human population but their role in disease is unknown. The investigations proposed are therefore directed toward determining the mechanism(s) by which reoviruses are responsible for the development of this well-defined arthritis and tenosynovitis of chickens. The primary emphasis of these studies is aimed at defining the molecular basis of avian reovirus pathogenicity and virulence. The role of individual viral structural proteins will be assessed by examination of the pathogenicity and cellular tropism of a selected group of recombinant viruses generated by dual infection with appropriate arthrogenic and non-arthrogenic reovirus isolates extensively characterized in vivo and in vitro. Additionally, production of arthrogenic variants of the standard mammalian reoviruses will be attempted by repeated passage of virus in human synovial cell culture and by selection of recombinants arising from mixed infection with known arthrogenic avian reoviruses. Subsequent examinations will permit correlation between specific structural proteins of these recombinant reoviruses and the observed cellular torpism and pathogenicity. Further studies will focus on the importance of the immune response, both humoral and cellular, in the promotion of the pathology observed. Finally, the biochemical mechanism(s) responsible for the marked gross and histopathologic changes evident are to be examined, with particular emphasis on the role of a specific protease, plasmin.